The purpose of this research is the elucidation of the biochemical processes responsible for the homeostasis of proteins in connective tissue. The mechanism of protein synthesis has been described and circumstantial evidence is available that protein synthesis and protein degradation are synchronized by some control mechanism. Investigations concentrating on the catabolic aspect of protein metabolism have been hampered by the unavailability of any information concerning the mechanism by which proteins are degraded or selected for degradation. A multiple attack on this problem is proposed. An intensive search for neutral proteases (endopeptidases) will be undertaken with the aid of endogenous and exogenous, natural and synthetic radioactive substrates. In addition surviving connective tissue slices will be subjected to a great number of conditions designed to induce intracellular protein breakdown. Such a system should enhance the chances to find enzymes that might be inhibited under physiological conditions as well as to find breakdown products of the action of such proteases. As a final approach the hormone (relaxin) structure will be determined completely. (The sequence of one of the two of the constituent chains has been completed). Using the chemically defined hormone or hormone-containing radioactive substitutions, attempts will be made to investigate the mode by which relaxin either increases the synthesis of collagen and protein polysaccharides or inhibits their degradation. BIBLIOGRAPHIC REFERENCES: Christian, Schwabe, J. Ken McDonald and Bernard G. Steinetz: Primary Structure of the A Chain of Porcine Relaxin. Biochem. Biophys. Res. Comm. 70:397, 1976. Christian Schwabe and S.A. Braddon: Evidence for One Essential Tryptophan Residue at the Active Site of Relaxin. Biochem. Biophys. Res. Comm. 68: 1126, 1976.